Final data from the Children’s Cancer Group (CCG) trial evaluating low-dose involved-field radiation therapy (IFRT) for patients with Hodgkin lymphoma achieving a complete response after chemotherapy show that at a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in event-free survival, but no improvement in overall survival. “For individual patients, the relative risks of relapse versus late effects of IFRT must be considered,” the researchers concluded. “Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.”

CCG 5942 randomized 498 patients achieving an initial complete response to chemotherapy to receive IFRT or no further therapy. Risk-adapted initial chemotherapy was based on stage, presence or absence of “B” symptoms, presence or absence of bulk disease, hilar adenopathy, and the number of involved nodal sites. Patients received four or six cycles of cyclophosphamide, vincristine, procarbazine (Matulane), and prednisone/doxorubicin, bleomycin, and vinblastine or six cycles of intensified chemotherapy including high-dose cytarabine and etoposide.

“A complete response to initial chemotherapy was defined as the resolution of all disease or at least 70% mass reduction in tumor volume in conjunction with a change from positive to negative on gallium scan,” the investigators explained, Patients who achieved a partial response were assigned to IFRT.

Interpreting the Results

At about 4 years, the investigators found a significant event-free survival difference favoring radiotherapy, and randomization was ended. “At that time, we could make no statements concerning any difference in survival because of the short follow-up for patients who experienced a relapse,” the investigators noted.

The updated study results show that in an as-treated analysis, the 10-year event-free survival rates were 91.2% for patients receiving IFRT vs 82.9% for those receiving no further therapy (P = .004), and the respective overall survival rates were 97.1% and 95.9% (P = .500). Bulk disease, B symptoms, and nodular sclerosis histology were risk factors for a lower event-free survival rate, the researchers reported in the Journal of Clinical Oncology.

“There are a number of ways in which these results could be interpreted,” the authors wrote. “It seems that, for every 100 patients who achieve a complete response to initial therapy, treatment with IFRT will prevent nine relapses. If the toxicity of IFRT is minimal, then all patients should receive [radiotherapy]. However, when the risk of late effects from [radiotherapy] is high, the risk-benefit ratio of IFRT must be reconsidered.”

The authors added that the choice of chemotherapy may also dictate the need for radiotherapy. “It has been shown that a more aggressive chemotherapy regimen may offset the potential benefit of the addition of [radiotherapy],” they wrote. “The dilemma is how to determine which treatment will yield the lowest toxicity because additional chemotherapy and low-dose [radiotherapy] are both associated with risk. These decisions will also be influenced by individual patient characteristics such as age, sex, and distribution of disease.”